Yongyong Ma

Quercetin suppresses the proliferation of multiple myeloma cells by down-regulating IQ motif-containing GTPase activating protein 1 expression and extracellular signal-regulated kinase activation

Abstract The flavonoid quercetin has shown anti-tumor effects against a variety of solid tumors. However, its effects on multiple myeloma (MM) remain unclear. In this study we examined the proliferation of human myeloma cell lines U266, KM3 and RPMI8226 and MM derived cells from four patients with MM after quercetin treatment, and detected the expression of IQ motif-containing GTPase activating protein 1 (IQGAP1), a scaffold protein involved in mitogen-activated protein kinase (MAPK) signaling, by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that quercetin inhibited the proliferation of MM cells in a dose- and time-dependent manner, accompanied by reduced IQGAP1 expression at mRNA and protein levels, and reduced extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Furthermore, we found that quercetin inhibited the interaction between IQGAP1 and ERK1/2 in RPMI8226 cells. In summary, our results suggest that quercetin suppresses the proliferation of MM cells by down-regulating IQGAP1 expression and ERK activation, and has potential as a novel agent to target oncogenic kinase cascades for MM therapy.

IQGAP1 plays an important role in the cell proliferation of multiple myeloma via the MAP kinase (ERK) pathway.

The present study was designed to explore the role of IQ motif-containing GTPase activating protein 1 (IQGAP1) in the cell proliferation of multiple myeloma (MM) via the MAP kinase (ERK) pathway. Reverse transcription‑polymerase chain reaction (RT-PCR) and western blot analysis were carried out to evaluate the expression of IQGAP1 in RPMI8226, U266 and KM3 cell lines and in primary MM cells from 4 MM patients. shRNA-expressing plasmids were used in RPMI8226 cells to knock down IQGAP1 and an MTT assay was used to examine the proliferative activity of the RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative and untransfected RPMI8226 cells in subgroups stimulated with VEGF/IL-6 or without. Western blot analyses were then performed to examine the protein levels of p-ERK1/2, ERK1/2, AKT, p-AKT, STAT3, p-STAT3 in the RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative and untransfected RPMI8226 cells. Co-immunoprecipitation was used to verify the interaction between the IQGAP1 scaffold and the MAP ERK kinase. We found that IQGAP1 was overexpressed in the human myeloma cell lines and in the patient MM cells. The proliferation rate in the RPMI8226 cells was decreased when IQGAP1 was knocked down with shRNA. IQGAP1 was found to affect RPMI8226 cell proliferation by regulation of the MAP kinase (ERK1/2) pathway; IQGAP1 scaffold-MAP kinase (ERK) interaction was noted in the human myeloma RPMI8226 cell lines. In conclusion, IQGAP1 plays an important role in the cell proliferation of MM via the MAP kinase (ERK) pathway.

Peripheral blood lymphocyte to monocyte ratio recovery from low levels at diagnosis after completion of first line therapy predicts good clinical outcomes in patients with diffuse large B-cell lymphoma

We retrospectively analyzed LMR at diagnosis and at completion of first-line therapy and prognosis in173 patients with DLBCL from 2005 to 2016. We found that patients with an LMR < 3.2 at diagnosis, as well as at completion of first-line therapy, had significantly lower PFS and OS rates than those with an LMR ≥ 3.2 (P<0.05). Patients with LMR that recovered from the low level at diagnosis showed superior overall survival (OS) (P=0.000) and progression-free survival (PFS) (P=0.001) compared with patients who failed to achieve a higher value at the completion of therapy. The multivariate analysis demonstrated that LMR values that did not increase upon completion of first-line therapy were an independent predictor for inferior OS (P=0.021) and PFS (P=0.046). In conclusion, LMR at diagnosis and at completion of first-line therapy is a simple biomarker to predict clinical outcomes in DLBCL. LMR recovery from low levels at diagnosis, irrespective of whether LMR reached the cutoff value, was associated with improved clinical outcomes.

Prognostic significance of the red blood cell distribution width in diffuse large B-cell lymphoma patients

This study examined the prognostic value of the baseline red blood cell distribution width (RDW) in diffuse large B cell lymphoma (DLBCL) patients. The associations between RDW and clinical characteristics were assessed in 161 DLBCL patients from 2005 to 2016. The log-rank test, univariate analysis, and Cox regression analysis were used to evaluate the relationship between RDW and survival. A RDW of 14.1% was considered to be the optimal cut-off value for predicting prognosis. A high RDW was associated with more frequent B symptoms (P=0.001), a higher International Prognostic Index score (P=0.032), more extranodal sites of disease (P=0.035), and significantly lower Eastern Cooperative Oncology Group performance status (P=0.031). The log-rank test demonstrated that patients with a high RDW had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P<0.001) and progression-free survival (PFS) (2-year PFS rate, 44.7% vs. 81.8%, P<0.001). The multivariate analysis demonstrated that RDW ≥14.1% was an independent predictor of OS (odds ratio [OR] = 0.345, P<0.001) and PFS (OR = 0.393, P=0.001). We demonstrated that a high RDW predicted an unfavorable prognosis in patients with DLBCL.

Association of proton pump inhibitors with the occurrence of gut-derived bacteraemia in patients with haematological malignancy after chemotherapy

Background: Gut-derived bacteraemia is a major complication in patients with haematological malignancy after chemotherapy. Objective: Our study aimed to investigate the role of proton pump inhibitors (PPIs) in the occurrence of gut-derived bacteraemia. Methods: We compared data from 92 hospitalized haematological malignancy patients after chemotherapy with gut-derived bacteraemia, collected from January 2009 to July 2015, with those of 92 contemporaneous, hospitalized haematological malignancy patients without bacteraemia. We evaluated PPIs use and analysed the effects of covariates. Results: Patients with gut-derived bacteraemia had a significantly higher incidence of PPIs use (69.6%) than that of controls (47.8%). Of the patients with gut-derived bacteraemia, only 44.6% had a documented indication for PPIs therapy. The antibacterial prophylaxis rate was 38.0% in the bacteraemia group and 58.7% in the non-antibacterial group. Based on multivariable logistic regression analysis, only PPIs use (P = 0.00, odds ratio (OR) = 0.546) was found to be associated with the risk of bacteraemia whereas antibacterial prophylaxis (P = 0.00, OR = 0.652) was protective. There were no significant differences in demographics, malignancy status, length of neutropenia, complications, or steroid use between the gut-derived bacteraemia and control group. Conclusions: This study suggests a potential association between PPIs use and development of gut-derived bacteraemia in haematological malignancy patients after chemotherapy.

Mean platelet volume predicts prognosis in patients with diffuse large B-cell lymphoma

To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B‐cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R‐CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut‐off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. Patients with MPV ≤ 9.1 fl experienced a shorter progression‐free survival (PFS) (2‐year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2‐year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.

Simultaneous occurrence of two B-cell malignancies: A case report

The present study describes the case of a 75-year-old male with coexisting multiple myeloma and diffuse large B-cell lymphoma. Although the two malignancies are mature B-cell neoplasms, their clinical manifestations are very different and the clinical approaches used to treat these two types of tumor vary. The patient in the present case was diagnosed with the simultaneous existence of two different B-cell tumors and was successfully treated using the DCEP regimen. The simultaneous presentation of two mature B-cell neoplasms, types of hematological malignancy, is very rare, thus the present case is considered to be interesting.